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Biomedical subjects

M B van 't Veer

Publications and source records attributed to M B van 't Veer.

At least 19 recordsLinked to original sources
PubMed2005

Short intensive sequential therapy followed by autologous stem cell transplantation in adult Burkitt, Burkitt-like and lymphoblastic lymphoma.

The feasibility and efficacy of up-front high-dose sequential chemotherapy followed by autologous stem cell transplantation (ASCT) in previously untreated adults (median age 33 years; range 15-64) with Burkitt lymphoma (BL), Burkitt-like lymphoma (BLL) or lymphoblastic lymphoma (LyLy), both without central nervous system or extensive bone marrow involvement was investigated in a multicenter phase II study. Treatment consisted of two sequential high-dose chemotherapy induction courses incorporating prednisone, cyclophosphamide, doxorubicin, etoposide and mitoxantrone, without high-dose methotrexate or high-dose cytarabine. Patients with at least PR went on with BEAM and ASCT. Protocol treatment was completed by 23/27 (85%) BL/BLL and 13/15 (87%) LyLy patients. Median treatment duration until BEAM was 70 (range: 50-116) days. No toxic deaths occurred. Response to treatment was complete response (CR) 81% and partial response (PR) 11% for BL/BLL, CR 73% and PR 20% for LyLy. At a median follow-up of 61 months of patients still alive, six BL/BLL and eight LyLy patients have died. The actuarial 5-year overall and event-free survival estimates are 81 and 73% for BL/BLL vs 46 and 40% for LyLy patients. In conclusion, this short up-front high-dose sequential chemotherapy regimen, followed by ASCT is highly effective in adults with BL/BLL with limited bone marrow involvement, but less so in patients with LyLy.

Adolescent↗
PubMed2003

Dynamics of circulating t(14;18)-positive cells during first-line and subsequent lines of treatment in follicular lymphoma.

In follicular lymphoma the t(14;18) might be useful as a tumor marker in predicting the quality of the response to treatment. We investigated whether analyzing numbers of t(14;18)-positive cells in peripheral blood correlated with remission status in individual patients receiving a variety of treatments. Numbers of circulating t(14;18)-positive cells were determined by real-time polymerase chain reaction (PCR) technique. Disease parameters and response to treatment were related to the pre- and post-treatment numbers of circulating t(14;18)-positive cells for 53 follicular lymphoma patients. In these 53 patients, 70 treatment episodes were investigated. A content of more than 328 t(14;18)-positive cells per 75,000 cells prior to therapy correlated with the more advanced stage IV disease ( P=0.01), bone marrow involvement ( P<0.01), and overt leukemic lymphoma ( P=0.04). Therapy episodes that cleared circulation from t(14;18)-positive cells with more than one log resulted in a significantly longer progression-free survival than treatment episodes with less than one log decline (26 versus 12 months, respectively) ( P<0.01). After first-line treatment episodes, numbers of circulating t(14;18)-positive cells declined in fairly all cases, irrespective of the clinical response. However, for second or later lines of treatment, declining numbers of lymphoma cells correlated with a clinical remission, whereas increasing numbers of lymphoma cells were associated with clinically stable or progressive disease. From this, we conclude that quantitation of circulating t(14;18)-positive cells in peripheral blood is of only limited clinical significance in predicting treatment efficacy for the individual follicular lymphoma patient.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2003

Immune and nonimmune causes of low recovery from leukodepleted platelet transfusions: a prospective study.

Alloantibodies against HLA antigens can be reduced by applying leukodepletion to transfusions. Because the importance of immunological and nonimmunological causes of poor platelet transfusion results using leukodepleted transfusions is not clear, we conducted a prospective study in an unselected patient population receiving leukodepleted transfusions. In 97 patients with hematological malignancies, 181 random leukodepleted platelet transfusions were studied for immunological causes of poor platelet transfusion results by calculating the odds ratio of four different screening tests for a low platelet recovery. Nonimmune causes were also studied by calculating the odds ratio of the most prevalent nonimmune causes for a low platelet recovery. No single screening test showed an association with recovery after 1 and 16 h following a platelet transfusion. The combination of a positive enzyme-linked immunosorbent assay (ELISA) and platelet immunofluorescence test (PIFT) or a combination of a positive lymphocyte immunofluorescence test (LIFT) and PIFT, demonstrating an association with a low platelet recovery after 16 h, was present in 2% of all platelet transfusions. Of nonimmune causes, splenomegaly and storage time of platelets for more than 3 days were associated with low platelet recovery after 1 h and 16 h of being present in 29% and 47% of all platelet transfusions, respectively. Immunological causes account for a small proportion of poor platelet transfusion results compared to nonimmunological causes in a nonselected patient population receiving leukodepleted transfusions.

Adolescent↗
PubMed2002

Increased levels of soluble CD27 in the cerebrospinal fluid are not diagnostic for leptomeningeal involvement by lymphoid malignancies.

Soluble CD27 (sCD27) reportedly is a sensitive and specific marker for leptomeningeal involvement (LI) of CD27-expressing lymphoproliferations such as B-cell non-Hodgkin's lymphoma (B-NHL) or chronic B-lymphocytic leukemia (B-CLL). Because morphological analysis of cerebrospinal fluid (CSF) in patients suspected of LI is false negative in one-third of patients, a diagnostic marker for LI by B-NHL or B-CLL would be very valuable. sCD27 was determined in the first CSF sample from each of 102 unselected patients submitted for (immuno)morphologic detection of malignant cells. The patients were considered to have LI if either (immuno)morphologic analyses showed tumor cells or if neuroradiological evaluation showed typical abnormalities consistent with LI. Patients were suspected of having LI if CSF samples revealed atypical lymphocytes and/or if clinical symptoms and signs suggestive of LI were present, but clinical follow-up was shorter than 3 months because of deterioration of the patient. LI was considered absent if (immuno)morphologic analyses of CSF samples were negative without evidence for LI during 3 months of clinical follow-up. In patients with chronic lymphoproliferative disorders [mainly B-non-Hodgkin's lymphoma (NHL)], sCD27 concentrations were significantly higher in the CSF samples of 16 patients with confirmed or suspected LI than in those of 46 patients without LI. However, sCD27 was also increased in a variety of other predominantly inflammatory neurological disorders including herpes simplex and zoster infections. The positive predictive value of sCD27 determination for LI was only 54%, but the negative predictive value was 92%. Normal sCD27 concentrations in CSF samples of patients with chronic lymphoproliferation makes LI unlikely, but the determination of CSF sCD27 is not sufficiently specific to serve as a reliable tumor marker.

Biomarkers, Tumor↗
PubMed2001

Cyclophosphamide, doxorubicin, vincristine and prednisone chemotherapy and radiotherapy for stage I intermediate or high grade non-Hodgkin's lymphomas: results of a strategy that adapts radiotherapy dose to the response after chemotherapy.

BACKGROUND: A limited number cycles of cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) chemotherapy followed by involved field radiotherapy is the treatment of choice for Ann Arbor stage I intermediate or high grade non-Hodgkin's lymphomas (NHL). The optimal radiotherapy dose in this combined modality setting, resulting in maximal disease control with minimal toxicity is unknown. In this retrospective single-center study we evaluated the results of a combined modality treatment strategy that adapts the radiotherapy dose to the response after chemotherapy, and focus on the influence of radiotherapy dose on local control and survival. PATIENTS AND METHODS: One hundred and forty patients with NHL Ann Arbor stages I/IE of intermediate or high grade malignancy received four cycles of CHOP chemotherapy followed by involved field radiotherapy (IF-RT). The radiotherapy dose for patients in complete response (CR) after CHOP was either 26 or 40 Gy. Patients in partial response (PR) after CHOP always received 40 Gy. The influence of the radiotherapy dose on treatment outcome was evaluated for patients in CR at the end of treatment (n=128). RESULTS: CR rates after chemotherapy and after radiotherapy were 67 and 91%, respectively. Seventy-four of the patients in CR after CHOP received 26 Gy, 20 patients in CR after CHOP 40 Gy. All patients in PR after CHOP (n=34) received 40 Gy. The localization of relapse (within or outside the radiation field) did not differ between patients receiving 26 or 40 Gy. Overall survival (OS) at 5 years for patients in CR after CHOP who received 26 and 40 Gy and for patients in PR after CHOP but CR after 40 Gy IF-RT was 76, 100 and 75%, respectively, (P=0.16), disease free survival (DFS) at 5 years 69, 90 and 75%, respectively, (P=0.52). CONCLUSIONS: No statistically significant differences in patterns of relapse or survival were found between patients receiving 26 or 40 Gy IF-RT, however the number of events in all subgroups was small.

Adult↗
PubMed2000

Molecular features responsible for the absence of immunoglobulin heavy chain protein synthesis in an IgH(-) subgroup of multiple myeloma.

This study involved 12 patients with multiple myeloma (MM), in whom malignant plasma cells did not contain immunoglobulin heavy chain (IgH) protein chains. Southern blot analysis revealed monoallelic J(H) gene rearrangements in 10 patients, biallelic rearrangement in 1 patient, and biallelic deletion of the J(H) and C(micro) regions in 1 patient. Heteroduplex polymerase chain reaction analysis enabled the identification and sequencing of 9 clonal J(H) gene rearrangements. Only 4 of the joinings were complete V(H)-(D)-J(H) rearrangements, including 3 in-frame rearrangements with evidence of somatic hypermutation. Five rearrangements concerned incomplete D(H)-J(H) joinings, mainly associated with deletion of the other allele. Curiously, in at least 1 of these 5 cases the second allele seemed to be in germline configuration, whereas the in-frame V(kappa)-J(kappa) gene rearrangements contained somatic mutations. The configuration of the IGH genes was further investigated by use of C(H) probes. In 5 patients the rearrangements in the J(H) and C(H) regions were not concordant, probably caused by illegitimate IGH class switch recombination (chromosomal translocations to 14q32. 3). These data indicate that in many IgH(-) MM patients illegitimate IGH class switch rearrangement or illegitimate deletion of the functional V(H)-(D(H))-J(H) allele are responsible for IgH negativity. For example, the exclusive presence of D(H)-J(H) rearrangements in combination with mutated IGK genes can only be explained in terms of normal B-cell development, if the second (functional) IGH allele is deleted, which was probably the case in most patients. Therefore, defects at the DNA level are responsible for the lack of IgH protein production in most IgH(-) MM patients.

Adult↗
PubMed1999

Platelet-bound immunogloblins before and after platelet transfusion: measurement of in vivo binding.

In routine tests to investigate immunological mechanisms as a cause for enhanced destruction of transfused platelets; serum from the patient is tested against a panel of donor lymphocytes and platelets to demonstrate the presence of antibodies against HLA or platelet specific antibodies. Here we describe a flow cytometric technique in which in vivo binding of immunoglobulins (Ig) is measured. By comparing the histograms of the platelet suspensions before and after transfusion, four different patterns were obtained: no Ig binding before and after transfusion (pattern 1), pre-existent Ig binding (patterns 2 and 3) or preferential Ig binding to the transfused platelets (pattern 4). This technique was tested in 164 random platelet transfusions and 34 HLA-matched platelet transfusions. A statistically significant association was found between pattern 1 and a negative result of the indirect platelet immunofluorescence test for the detection of antibodies in the serum taken before the transfusion studied or a good platelet recovery and between pattern 4 and a positive indirect platelet immunofluorescence test or a low platelet recovery.

Autoimmunity↗
PubMed1998

A phase I/II study of multicyclic dose-intensive chemotherapy supported with G-CSF, or G-CSF and haematopoietic progenitor cells in whole blood, in two consecutive cohorts of patients.

We investigated the reconstitutive potential of haematopoietic progenitor cells collected in autologous whole blood during multicycle dose-intensified chemotherapy. Forty patients with metastatic solid tumours were treated with up to six cycles of cisplatin and escalating doses of ifosfamide every 14 days. Cisplatin was administered in 3% sodium chloride over 3 h, followed by ifosfamide over 24 h and mesna over 36 h. The first cohort of patients received granulocyte colony-stimulating factor (G-CSF) days 4-14. Once dose-limiting toxicity was reached in cohort 1, the study continued with a second cohort of patients, in whom, in addition to G-CSF on days 4-14, 500 ml of G-CSF and chemotherapy-'primed' whole blood was collected on day 15, i.e. on day 1 of treatment cycles two to six, before cisplatin administration. This volume of blood was kept unprocessed at 4 degrees C and reinfused 20-24 h after the completion of ifosfamide. In cohort 1, dose-limiting toxicity (DLT) was reached at ifosfamide 6.0 g m(-2) with two out of six of the patients developing neutropenic fever. Although in cohort 2 no neutropenic fever was encountered, neither the frequency nor the duration of grade 4 neutropenia and thrombocytopenia were reduced. Cumulative asthenia resulted in DLT at 7.0 g m(-2). The median number of CD34+ cells in 500 ml of whole blood after the first cycle (i.e. at start of cycle 2) was 1.15 x 10(6) kg(-1). This number was significantly greater after the second cycle (2.06 x 10(6) kg(-1), P = 0.01) and then gradually decreased after cycles three to six. After storing whole blood, the number of CD34+ cells had not decreased (median + 10%). We conclude that the method of combined bone marrow support by G-CSF and haematopoietic progenitor cells in autologous whole blood collected before each cycle of a 2-weekly regimen of cisplatin-ifosfamide does not result in clinically measurable reduced bone marrow toxicity compared with what can be expected by the use of G-CSF alone.

Adult↗
PubMed1996

[Successful ambulatory treatment of patients with hairy-cell leukemia using one cycle of the purine analog cladribine. 'Hemato-oncologic volwassen Nederland' (HOVON) Study Group].

OBJECTIVE: To study the efficacy of a single cycle of 2-chlorodeoxyadenosine (2-CDA) given as a 2-hour infusion on 5 consecutive days, in patients with hairy cell leukaemia (HCL). DESIGN: Non-randomised phase II study in an unselected population. SETTING: 20 centres in the Netherlands and Belgium. METHODS: Response to treatment was evaluated in 23 patients with a minimum follow-up of 6 months. All patients had proven HCL, were untreated or pretreated with splenectomy and (or) IFN alpha, and had at least one of the following criteria: Hb < 7.3 mmol/l, neutrophils < 1.0 x 10(9)/l, platelets < 100 x 10(9)/l, systemic symptoms or symptomatic splenomegaly. Patients with an active infection were ineligible. Treatment consisted of one cycle of 2-CDA (2-hour i.v. infusion days 1-5, dosage 0.1 mg/kg/day). RESULTS: Sixteen patients had received no prior treatment. At the 4-week evaluation, most patients (17/23) had improvement in one or two haematological parameters. After 6 months, 6/23 (26%) patients were in haematological remission and 13/23 (57%) were in complete remission. No patient developed progressive disease. Febrile neutropenia developed in 12/23 (52%) patients, with documented infection in three of them. A generalised rash was seen in 9/23 (39%) patients. CONCLUSION: 2-CDA appears to be the treatment of choice in patients with HCL. With a single 5-day cycle, over 80% of patients achieved remission.

Antineoplastic Agents↗
PubMed1995

AML-MO: clinical entity or waste basket for immature blastic leukemias? A description of 14 patients. Dutch Slide Review Committee of Leukemias in Adults.

In the period from August 1991 to August 1994, the Dutch Slide Review Committee of Adult Leukemias classified 14 leukemias as AML-M0. We reviewed the clinical characteristics and response to therapy of these patients. Eight patients were male. Patients' age ranged from 7 to 77 years (medium age 62 years). There was a striking homogeneity in morphological appearance of the blasts, being small to medium-sized round cells with often an eccentric nucleus with fine chromatin, several distinct nucleoli, and a high nucleo-cytoplasmic ratio. In addition to myeloid-associated markers such as CD13 and CD33, the blasts of all patients were positive for CD34 and HLA-DR, pointing to their immature differentiation stage. TdT was present in the blasts of 71%, CD7 was positive in the blasts of 42% of the patients. No consistent cytogenetic abnormalities were found. With respect to the treatment outcome, four patients achieved a complete remission after remission-induction treatment. The median survival was 4.5 months. Our present study shows AML-M0 to be an immature leukemia, uniform in morphology and immunological phenotype, with no consistent cytogenetic phenotype and with a poor clinical outcome.

Acute Disease↗
PubMed1994

Acquired von Willebrand disease caused by an autoantibody selectively inhibiting the binding of von Willebrand factor to collagen.

An 82-year-old man with a low-grade malignant non-Hodgkin lymphoma and an IgG3 lambda monoclonal gammopathy presented a recently acquired bleeding tendency, characterized by recurrent epistaxis, easy bruising, and episodes of melena, requiring packed red blood cell transfusions. Coagulation studies showed a von Willebrand factor (vWF) defect (Ivy bleeding time, > 15 minutes; vWF antigen [vWF:Ag], 0.08 U/mL; ristocetin cofactor activity [vWF:RCoF], < 0.05 U/mL; collagen binding activity [vWF:CBA], 0.01 U/mL; absence of the high molecular weight multimers of vWF on multimeric analysis). Mixing experiments suggested the presence of an inhibitor directed against the vWF:CBA activity of vWF without significantly inhibiting the FVIII:C, vWF:Ag, and vWF:RCoF activities. The inhibitor was identified as an antibody of the IgM class by immunoabsorption of vWF and inhibitor-vWF complexes from the plasma of the patient. Subsequent immunoprecipitation experiments using recombinant fragments of vWF showed that the inhibitor reacted with both the glycoprotein Ib binding domain (amino acids [aa] 422-826) and the A3 (aa 909-1112) domain of vWF, but not with the A2 (aa 716-908) or D4 (aa 1183-1535) domains. We conclude that the IgM autoantibody inhibits the vWF:CBA activity by reacting with an epitope present on both the glycoprotein Ib and A3 domains of vWF.

Aged↗
PubMed1994

Effectiveness of high-dose intravenous gamma globulin therapy in acquired von Willebrand's disease.

An 82-year-old patient with acquired von Willebrand's disease in association with a non-Hodgkin's lymphoma and a benign IgG-lambda monoclonal paraproteinemia is described with severe recurring nasopharyngeal bleedings, who responded poorly to desmopressin (DDAVP) and factor VIII/von Willebrand factor concentrates but was successfully treated with high-dose e intravenous gamma-globulin therapy.

Aged↗
PubMed1994

Genomic organization of the translocations (8;14) and (14;18) in a new lymphoma cell line.

We generated a new lymphoma cell line carrying the translocations (8;14) and (14;18) and studied the genomic organization and expression of the BCL-2 and MYC genes. Polymerase chain reaction (PCR) and Southern analysis showed that the breakpoints of t(14;18) were located in the major breakpoint region (mbr) of the BCL-2 gene and just 5' of JH6 in the IgH locus. The breakpoints of the t(8;14) were located upstream of exon 2 in the non-coding region of the MYC gene and near the switch region of the IgH locus. Both IgH loci were involved in chromosomal translocations resulting in the absence of a functional B-cell receptor. Normal BCL-2 and truncated MYC transcripts were detected in these cells. The BCL-2 protein was expressed.

Aged↗
PubMed1993

Clinical features of CD30 (Ki-1) positive anaplastic large-cell lymphoma (ALCL). Review of the literature.

CD30-positive anaplastic large cell lymphoma (ALCL), also known as Ki-1 lymphoma, was first described in 1985 as a new histological subtype, and was added to the updated Kiel classification in 1988. It is regarded as a process of high-grade malignancy, mainly on histological grounds. This review describes clinical features in 255 patients. There is a bimodal age distribution, with peaks in adolescence and old age. The male/female ratio is approximately 3:2. About one-third of patients present with extranodal disease. Especially the skin is often involved (two-thirds of all extranodal localisations). The tumours generally have an aggressive clinical behaviour, as in other lymphomas of high-grade malignancy. Especially the high relapse rate seems responsible for the unfavourable prognosis in these patients. However, patients with disease limited to the skin (skin-only presentation) tend to have a slower, protracted course, recalling that of the low-grade lymphomas. We conclude that, also on clinical grounds, CD30-positive ALCL is a distinct entity, in which, based on localisation of the disease, two subgroups can be discriminated with different clinical behaviour.

Adolescent↗
PubMed1992

Detection of residual disease in translocation (14;18) positive non-Hodgkin's lymphoma, using the polymerase chain reaction: a comparison with conventional staging methods.

This paper reports the detection of residual lymphoma cells in blood and bone marrow samples from patients with translocation (t) (14;18) positive non-Hodgkin's lymphoma by the polymerase chain reaction (PCR) compared with conventional staging techniques. In 15 of 22 samples, in which no lymphoma cells could be detected by morphological examination, t(14;18) positive cells were detected by PCR. In 13 of 21 samples, in which a monoclonal B-cell population was not detectable by immunological marker analysis, PCR was positive. The clinical status (physical examination, imaging techniques, leucocyte count, and occasionally morphology and immunological marker analysis) was documented in 30 patients at the time of PCR analysis. In three of 19 patients with clinical evidence of disease, circulating t(14;18) positive cells were not detectable by PCR. Five of 11 patients in clinical remission from 7 to 47 months, showed t(14;18) positive cells in the blood. Our data show that PCR analysis in t(14;18) positive non-Hodgkin's lymphoma offers a powerful tool in the study of residual disease.

Biomarkers, Tumor↗
PubMed1990

Electron microscopy: a contribution to further classification of acute unclassifiable childhood leukemia.

The ultrastructural, light microscopical and immunological features of twelve cases of acute childhood leukemia are described. Nine cases were unclassifiable by light microscopy, morphology and cytochemistry, and three were difficult to classify because of a low percentage of Sudan-Black B positive blasts. By means of electron microscopy (including peroxidase cytochemistry), two main groups were seen: 1. Acute myeloid leukemia, in which could be distinguished a) a more differentiated myeloid leukemia, b) a leukemia with megakaryoblastic involvement and c) a minimally differentiated acute myeloid leukemia with granules present and 2. lymphoblastic leukemia. One case could not be classified. The first group included two possible cases of a hybrid leukemia with CD19 or CD10 positivity as well as ultrastructural peroxidase activity. We conclude that electron microscopy aids to further classification of minimally differentiated and hybrid acute leukemias.

Adolescent↗